1115P - Comparison of efficacy and toxicity of dabrafenib/trametinib versus vemurafenib/cobimetinib therapy in routine medical practice: Eight years of BRAF/MEK inhibitor use in routine clinical practice

Background

BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) significantly changed the prognosis of patients with advanced melanoma. Our aim was to compare long-term treatment outcomes in patients treated with vemurafenib + cobimetinib (V+C) and dabrafenib + trametinib (D+T) in real world practise.

Methods

Consecutive patients with unresectable or metastatic BRAF-mutated melanoma started treatment with V+C and D+T between 01/Jan/2014 and 30/Jun/2021 according to national drug reimbursement programme. Clinical factors including age, sex, primary location of melanoma, ECOG performance status, baseline LDH level, metastasis location, response to treatment, adverse events (AEs) were analysed. Survival analyses were performed using the Kaplan-Meier method, Log-rank and chi-square tests were used for comparison between groups.

Results

In total 583 patients were enroled, 178 (31%) received first-line V+C, while 405 (69%) D+T. The patients with V + C were significantly younger (median 56 vs 62; p=0.0001) and had more frequent brain metastases (40% vs 30%, p = 0,023). The estimated median OS (mOS) in V+C group was 12.0 month while in D+T - 12.5 months (p=0.79; HR=1.03, Cl 95% 0.8-1.3). The estimated progression free survival (mPFS) group V+C was 7.8 month while in D+T - 7.2 months (p=0.81; HR=1.02, Cl 95% 0.8-1.2). 5- and 7-years OS rates was 21%/19% and 17%/13% and PFS rates 11%/11% and 8%/8% in V+C and D+T group, respectively. In multivariate analysis a significant positive effect on OS and PFS had normal LDH level, no brain metastases and ECOG 0 in both groups, in addition only in D+T group a significant positive effect on OS had age ≥ 65 years. The percentage of patients with any grade of AEs was similar in boths groups (p=0,8088). Skin AEs and nephrotoxicity were more frequent in V+C group (p=0.0004 and p=0.01, respectively); fever were more frequent in D+C group (p = 0.035).

Conclusions

The analysis did not show differences in median OS and PFS between patients treated in the first line with V+C and D+T. In the V+C group there were more skin AEs and nephrotoxicity, and in D+T fever was more common, however the treatment was well tolerated in nonselected patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

B. Cybulska-Stopa: Financial Interests, Personal, Advisory Board, Advisory Boards outside of the scope of the study: BMS, Novartis, Roche, Pierre Fabre, MSD; Financial Interests, Personal, Invited Speaker: BMS, Novartis, Roche, Pierre Fabre, MSD. A.M. Czarnecka: Financial Interests, Personal, Advisory Board, Advisory Boards outside of the scope of the study: BMS, Novartis, Roche, Merck; Financial Interests, Personal, Invited Speaker: BMS, Novartis, Roche, Merck. M. Ziętek: Financial Interests, Personal, Advisory Board, Advisory Boards outside of the scope of the study: BMS, MSD, Novartis; Financial Interests, Personal, Invited Speaker: BMS, MSD, Novartis. L. Galus: Financial Interests, Personal, Advisory Board, Advisory Boards outside of the scope of the study: BMS, Roche, MSD, Novartis, Pierre Fabre; Financial Interests, Personal, Invited Speaker: BMS, Roche, MSD, Novartis, Pierre Fabre. W. Bal: Financial Interests, Personal, Advisory Board, Department of Clinical Oncology: BMS, Novartis, Roche, Pierre Fabre, MSD; Financial Interests, Personal, Invited Speaker: BMS, Novartis, Roche, Pierre Fabre, MSD. T. Kubiatowski: Financial Interests, Personal, Advisory Board, Advisory Boards outside of the scope of the study: BMS, Novartis, Roche, Pierre Fabre, MSD; Financial Interests, Personal, Invited Speaker: BMS, Novartis, Roche, Pierre Fabre, MSD. G. Kaminska-Winciorek: Financial Interests, Personal, Advisory Board, Advisory Boards outside of the scope of the study: BMS, Novartis, Roche, Pierre Fabre, MSD; Financial Interests, Personal, Invited Speaker: BMS, Novartis, Roche, Pierre Fabre, MSD. R. Suwinski: Financial Interests, Personal, Advisory Board, Advisory Boards outside of the scope of the study: BMS, MSD, Astellas Pharma; Financial Interests, Personal, Invited Speaker: BMS, MSD, Astellas Pharma. J. Mackiewicz: Financial Interests, Personal, Research Grant: BMS, BMS; Financial Interests, Personal, Speaker, Consultant, Advisor: MSD, MSD; Financial Interests, Personal, Advisory Board, Advisory Boards outside of the scope of the study: GSK, Roche, Novartis, Pierre Fabre; Financial Interests, Personal, Invited Speaker: GSK, Roche, Novartis, Pierre Fabre. R. Dziura: Financial Interests, Personal, Advisory Board, Advisory Boards outside of the scope of the study: BMS, Novartis, Roche, Pierre Fabre, MSD; Financial Interests, Personal, Invited Speaker: BMS, Novartis, Roche, Pierre Fabre, MSD. N. Kempa-Kaminska: Financial Interests, Personal, Advisory Board, Advisory Boards outside of the scope of the study: BMS, Roche; Financial Interests, Personal, Invited Speaker: BMS, Roche. P. Rutkowski: Financial Interests, Personal, Invited Speaker, honoraria for lectures: MSD, BMS, Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre, Merck, Sanofi, Blueprint Medicines, Philogen; Financial Interests, Personal, Invited Speaker: Merck, Sanofi, Novartis, AstraZeneca; Financial Interests, Institutional, Research Grant, research grant for ISS: Pfizer; Financial Interests, Institutional, Funding, research grant for institution: BMS; Non-Financial Interests, Member of Board of Directors: Polish Society of Surgical Oncology; Non-Financial Interests, Member of Board of Directors, President: Polish Oncological Society. All other authors have declared no conflicts of interest.